From the Guidelines
Azathioprine monitoring requires regular laboratory tests, including full blood count (FBC) and liver function tests (LFTs), to detect potential toxicity.
Monitoring Frequency
- Initially, weekly monitoring of FBC and LFTs is recommended for the first 4-8 weeks of treatment, as suggested by the British National Formulary and the azathioprine datasheet 1.
- After the initial period, the frequency of monitoring can be reduced to at least once every 3 months for patients on a stable dose 1.
- However, more frequent monitoring is advised for patients with higher dosages, hepatic or renal impairment, or those with low TPMT activity 1.
Laboratory Tests
- FBC is essential to monitor for myelosuppression, a common adverse effect of azathioprine 1.
- LFTs are necessary to detect hepatotoxicity, a recognized complication of azathioprine therapy 1.
- Serum amylase should be measured in patients with acute abdominal pain and/or severe vomiting to rule out acute pancreatitis, a rare but well-recognized side-effect of azathioprine 1.
Patient Education
- Patients on azathioprine should be instructed to report immediately any evidence of infection, unexpected bruising or bleeding, or jaundice 1.
From the FDA Drug Label
Patients on AZASAN should have complete blood counts, including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary. TPMT and NUDT15 Testing: Consider genotyping or phenotyping patients for TPMT deficiency and genotyping for NUDT15 deficiency in patients with severe myelosuppression.
The necessary laboratory tests to monitor while on azathioprine (Imuran) include:
- Complete Blood Count (CBC): weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if necessary
- Platelet counts: as part of the CBC
- TPMT and NUDT15 testing: consider genotyping or phenotyping for TPMT deficiency and genotyping for NUDT15 deficiency in patients with severe myelosuppression 2
From the Research
Laboratory Tests for Azathioprine Monitoring
To monitor patients on azathioprine (Imuran), several laboratory tests are necessary:
- Blood count monitoring to detect myelotoxicity, which can occur even in patients with normal thiopurine methyltransferase (TPMT) activity 3, 4
- TPMT enzyme activity testing to predict life-threatening myelotoxicity in patients who are TPMT-deficient 3
- Measurement of 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) concentrations to determine why a patient is not responding to a standard dose of azathioprine and to help avoid myelosuppression 3, 5, 6
- Monitoring of metabolites, such as 6-TGN and 6-MMP, to assess drug metabolism and optimize drug dosing with minimized drug-induced toxicity 6
Rationale for Laboratory Tests
The rationale for these laboratory tests is based on the complex metabolism of azathioprine and the genetic polymorphisms in metabolizing enzymes, which can lead to a wide inter- and intra-patient variation in the concentrations of active and toxic metabolites 3. Additionally, severe bone marrow suppression can occur with azathioprine, and frequent monitoring of blood counts is necessary to avoid this complication 4.
Frequency and Timing of Laboratory Tests
The frequency and timing of these laboratory tests may vary depending on the individual patient and their response to azathioprine treatment. However, it is recommended that patients on azathioprine have regular blood count monitoring and TPMT enzyme activity testing, especially when initiating treatment or adjusting the dose 3, 4, 6. Measurement of 6-TGN and 6-MMP concentrations may be necessary in patients who are not responding to treatment or who are experiencing adverse effects 3, 5, 6.